This invention relates to a process and an apparatus for forming capsules, for example for the delivery of pharmaceuticals, and also to the resulting capsules.
A variety of pharmaceuticals and other materials are delivered in capsules. Where the material is a particulate material such as a powder it may be enclosed in a hard capsule, typically of elongated round-ended cylindrical shape, made in two pieces for assembly around the material. Both liquid and particulate material may be enclosed in soft capsules, these capsules being made from films of a soft elastic polymer which are brought together between rotating dies that have cavities in their surfaces. The material to fill the capsules is supplied between the films as the films deform into the cavities; as the dies move the films come together and are sealed together by application of heat and/or pressure at the dies. Both types of capsules are commonly made from gelatin films. The bonding of thermoplastic polymer films using dielectric heating (or radio frequency heating) has also been known for many years. In this process the two pieces of thermoplastic material are positioned between opposed electrodes (or one electrode and a base plate), the electrodes are pressed together, and a radio frequency voltage is applied between the electrodes. This process is however applicable only to those materials which have a significant dielectric loss index, for example greater than 0.2, over the range say 20-60 MHz, for example polyvinylchloride. Dielectric welding has not hitherto been considered suitable for welding the water-soluble polymers which are desirably used in making capsules for pharmaceuticals.
The use of dielectric heating in making capsules from a thermo-weldable material is described by Lavaud in GB-A-908 344, the strips of film passing between moulds into which the films are sucked to form opposing recesses, the recesses then being filled with a material to be encapsulated, and the films then being welded together by applying a high frequency electric current between the moulds. The capsules can then be cut from the strip. The use of films other than gelatin to encapsulate medicines has also been known for many years, for example from U.S. Pat. No. 4,154,636 (Motoyama et al.), the films being bonded by thermal adhesion with an electrical impulse heater; this document mentions water-soluble polymers such as hydroxypropyl methyl cellulose, and also polymers that can be digested. Similarly EP-A-0 211 079 describes the manufacture of two-compartment soft capsules made of films that may be of gelatin, or hydroxypropyl methyl cellulose phthalate mixed with gelatin for example to provide different solubilities.
According to the present invention there is provided a process for making capsules, the process using two films of a water-soluble polymeric material, and the process comprising the steps of deforming the films to form a multiplicity of recesses, filling the recesses with a flowable filling material, welding the films together by dielectric welding at a welding location to form a multiplicity of enclosures containing the filling material, and cutting the filled enclosures from the remaining parts of the films so as to form a multiplicity of capsules.
The films may be subjected to the said steps at a plurality of different locations, or at a single location. Performing all these steps at a single location avoids any problems with registration of the recesses with the welding or cutting means. The welding location is defined by two opposed electrodes, which can be pressed together, and to which a power supply means can provide a high frequency electrical supply.
The supply may in principle be at a frequency between 1 MHz and 200 MHz, usually between 10 MHz and 100 MHz, but stringent limits are imposed on any emitted radio waves. In practice therefore the choice of frequency may be more limited. For example the supply frequency may be 27.12 MHz, or 40.68 MHz. A tuned circuit may be electrically connected to at least one of the electrodes, for example the tuned circuit may be connected between one electrode and ground potential. For example a tuned circuit comprising an inductor and a capacitor in series may be connected between one electrode and ground potential, the tuned circuit preferably resonating at a frequency substantially that of the supply.
The electrodes defining the welding location are preferably movable towards and away from each other, to allow the films to be held and pressed between them. A heater may be associated with at least one of the electrodes, to provide heating of the films. At least one of the electrodes may comprise recesses complementary to the shape of the recesses defined in the films. Retaining means may be provided for retaining the films against the or each electrode during welding, and the retaining means may operate by suction.
The polymeric films are preferably formed into a bag before welding, and the filling material is introduced into the bag prior to welding. At least one seam of the bag may be formed by welding together the films, and this welding may be performed using heat, or by dielectric welding. One seam of the bag may be formed by folding a wider film of the polymeric material to define two opposed films. The recesses may be formed by moulding, preferably by placing the films against a mould having a multiplicity of cavities corresponding to the shapes of the recesses to be formed. The films may be moulded by suction into the cavities. The material may be softened prior to moulding, for example by heating. As indicated earlier, the several steps of the process may be performed at the same location, in which case the moulding recesses would be defined in the welding electrodes. The cutting out of the capsules is preferably performed by punching, and the punches may also be incorporated in the welding electrodes.
The filling material may be a pharmaceutical, and is a preferably a liquid. The polymeric material may be polyvinyl alcohol, which is water-soluble and biodegradable, though not edible. Where the capsules are intended to be swallowed (for example where they contain a pharmaceutical or a nutritional supplement), the polymeric material should be edible. It may for example be gelatin, or a water-soluble cellulose derivative. For example it may be hydroxypropyl methyl cellulose, which is approved for use with pharmaceuticals and in food (being indicated by the code E464 in Europe). The polymeric material must not contain any harmful or toxic additives, but may contain compounds such as glycerol (E422), glycerol mono-, di- or tri-acetate, or glycerol monostearate (E471) as plasticisers, these compounds also being edible and dispersible or soluble in water. It may also contain a preservative such as methyl 4-hydroxy-benzoate (E218). Other suitable cellulose derivatives are hydroxypropyl cellulose (E463), and methyl ethyl cellulose (E465).
The invention also provides an apparatus for making and filling capsules by the method specified above, comprising one or more stations operable to implement sequentially the steps of the method specified above. In a further aspect, the invention provides a capsule formed by the method or apparatus of the invention.